Stimulation of the α7 Nicotinic Acetylcholine Receptor Protects Against Acute Lung Injury Induced by Surfactant Depletion
Stimulation of the α7 Nicotinic Acetylcholine Receptor Protects Against Acute Lung Injury Induced by Surfactant Depletion
Hossein fatemikia,1,*Farzaneh Ketabchi,2
1. Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 2. Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Introduction: The cholinergic anti-inflammatory pathway (CAP) has been identified as a key regulator of inflammatory responses in several animal models of lung injury. The alpha7 nicotinic acetylcholine receptor (α7nAChR) is a crucial component of this pathway. This study aimed to determine the role of α7nAChR in a saline-lavaged rat model of acute lung injury. To investigate this, nicotine was administered as an agonist, while Methyllycaconitine citrate (MLA) was used as an antagonist of α7nAChR.
Methods: Male Sprague Dawley rats were divided into four groups: Sham, saline lavage (LAV), LAV treated with nicotine (LAV+NIC), and LAV treated with both nicotine and MLA (LAV+NIC+MLA). Tracheostomy and catheterization of the femoral artery were performed under deep anesthesia. The animals were subjected to volume-controlled ventilation and lung injury through 10 repeated saline lavages (30 ml saline at 37 °C). The recovery phase lasted for 3 hours, and drugs were injected 1 hour after the last lavage. We assessed mean blood pressure (MBP), heart rate (HR), maximal inspiratory (MIP) and expiratory (MEP) airway pressures, gas exchange across the blood-gas barrier, lung compliance, immune cell counts in the blood and bronchoalveolar lavage (BAL), malondialdehyde (MDA) levels, and lung histological scores.
Results: MBP, HR, PaO2, PaO2/FiO2 ratio, and pH decreased, whereas MIP and MEP, and PaCO2 increased 1 hour after the saline lavage. Nicotine corrected entirely all the above parameters in the LAV+NIC group. MLA prevented the effects of nicotine on the above parameters, except that MLA had no extra effect on MIP or MEP. In addition, nicotine improved lung compliance in the LAV+NIC group, though it was inhibited by MLA in the LAV+MLA+NIC group. The increases of plasma and lung tissue MDA in the LAV group were diminished by nicotine, whereas, MLA prevented these reductions. Total BAL cell count and lung histological scores were attenuated by nicotine in the LAV+NIC group, whereas, MLA reversed the mentioned alterations in the LAV+MLA+NIC group.
Conclusion: These findings highlight that nicotine exerts a protective anti-inflammatory effect in lung injury induced by saline lavage through the cholinergic α7nAChR pathway.